Real Madrid captain Sergio Ramos and left-back Marcelo are both set for spells on the sidelines, starting with Wednesday's Champions League game at Shakhtar Donetsk.
Ramos played in Saturday's 4-0 Clasico defeat at home to Barcelona but had to take a pain-killing injection due to the shoulder injury that has troubled him over the last two months.
Marcelo, meanwhile, had also been a doubt for that game due to a hamstring issue and limped off midway through the second half after appearing to have suffered a recurrence of the problem.
Both defenders have been left out of the Madrid squad that travelled to the Ukraine as Rafa Benitez's side look to secure top spot in Champions League Group A and bounce back from a run of two consecutive defeats.
Marcelo is expected to be out for two to three weeks after a club statement confirmed that tests had shown the Brazil international had more adductor trouble.
"Following the tests carried out on Marcelo today in the Sanitas la Moraleja University Hospital, the player has been diagnosed with an injury in his left adductor muscle," the statement said. "His recovery will continue to be assessed."
Ramos' situation is less clear, with the club yet to issue a statement on his condition, but Marca reports that the centre-back is keen to avoid surgery and hopes that spending several weeks on the sidelines will allow him to recover.
- Sergio Ramos (@SergioRamos) November 23, 2015
Ramos posted on Twitter on Wednesday to express his hope that the team would be able to recover their form in his absence.
"We only look back to learn from our mistakes and gather strength for tomorrow," the Spain international wrote.